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Know Your Naloxone: Save a Life

Medically reviewed by L. Anderson, PharmD Last updated on Apr 25, 2019.

The Opioid Overdose Reality

On average, 130 Americans die every day from an opioid overdose, based on 2019 data from NIDA. That equates to one person every 11 minutes.

Opioids are a class of drugs that include narcotic analgesic prescription medications such as:

In the US, the death rate from prescription opioid overdoses has increased over 4-fold since 1999, while deaths from heroin deaths have more than quadrupled since 2010. As noted by the NIDA, in 2017 more than 47,000 Americans died as a result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl, a powerful synthetic opioid.

Heroin, an illicit and highly addictive drug, is increasingly found on the streets contaminated with fentanyl smuggled in from China and Mexico.

In response, several state and federal initiatives are underway to combat this epidemic, and $3.2 billion in federal money was allocated in 2018 for this fight. Even the U.S. Surgeon General in April 2018 urged Americans to have naloxone on hand for emergency situations. It is now available at most U.S. pharmacies without a prescription.

The FDA has also approved new naloxone agents that can reverse the depressed, often fatal slowed breathing (respiratory depression) that can occur with a narcotic overdose. These agents can be easily administered by emergency personel, families, friends or even bystanders to anyone experiencing an opioid overdose. Generic naloxone nasal spray was approved in 2019.

How Do I Recognize an Opioid Overdose?

All opioids (narcotics) will produce various levels of central nervous system (CNS) depression and side effects such as drowsiness, sedation, and slowed breathing. In an overdose, you might notice stupor, coma, slurred speech, clammy skin, pinpoint pupils, and low blood pressure.

The most dangerous and often fatal side effect of an opioid overdose is respiratory depression - slowed or arrested breathing. This risk is multiplied when the narcotic is combined with alcohol or other CNS depressants.

If you believe someone has overdosed on narcotics, call 911 immediately. A reversal agent called naloxone can be life-saving for patients who overdose on narcotics, although in patients dependent upon opioids, it can also cause a severe withdrawal effect.

What is Naloxone?

Naloxone is a medication that rapidly reverses the effects of an opioid (narcotic) overdose and is the standard treatment.

Naloxone has been available in injection form to reverse the effects of opioid overdose for more than 40 years. It is not addictive or considered an opioid itself. Prior naloxone treatments required administration via a syringe and needle and were most commonly used by trained medical personnel and emergency responders.

Today, newer naloxone approvals come as nasal sprays and auto-injectors to make these life-saving drugs more user-friendly.

In fact, most states have now passed legislation designed to improve lay-person naloxone access.

A generic nasal spray is now approved, too.

How Can Naloxone Save a Life?

Pharmacologically, naloxone is considered an opioid antagonist, meaning it blocks opioid receptors.

Unlike opioids, naloxone (brand names include Narcan, Narcan Nasal, Evzio) is not a controlled substance and has no potential for abuse.

In fact, naloxone has no pharmacologic action in the absence of an actual opioid overdose. It is regularly used by first responders and can be administered by lay-people with little or no training.

Naloxone can counter overdose effects, including depressed breathing, drowsiness, and loss of consciousness - usually within 2 to 3 minutes - and can be given by family members or caregivers until emergency help arrives. In families or friends that elect to carry the devices or store these medications in their home, learning how to use them ahead of time may save time.

What Are Opioids?

Naloxone reverses the effects of prescription opioid overdoses, as well as heroin, but has no action in other types of overdoses such as benzodiazepines like alprazolam (Xanax) or lorazepam (Ativan), sedatives like barbiturates, or alcohol.

You should always call for emergency help when you use naloxone; you may not know what the person has overdosed on, or it may be a mixture of substances. Examples of prescription opioids that may be involved in an overdose include:

If drugs have been purchased on the street, they could contain added narcotics, benzodiazepines, or other unknown toxic chemicals.

Narcan: The Original

The first FDA-approved naloxone was injectable Narcan which became available in the early 1970's.

The intravenous formulation is used in clinic and hospital settings, but an intramuscular formulation is available also, often sold in a kit with 2 syringes and 2 vials of 0.4 mg/mL naloxone and provided to emergency first-responders. The naloxone vials are also sold in a kit with nasal atomizers for use as a nasal spray. All kits contain an instruction chart for use and assembly direction.

The FDA-approved Evzio Autoinjector and Narcan Nasal Spray are now available at pharmacies but at higher costs. Narcan Nasal Spray has been approved in 2 mg and 4 mg strengths.

Patients who cannot afford these branded medications should call the US manufacturers to determine if they qualify for assistance, or if other pricing discounts or coupons are possible.

In 2019, a generic version of Narcan Nasal Spray, known as naloxone nasal spray, was approved and should lead to significant cost-savings.

Evzio (naloxone hydrochloride) Autoinjector

In April 2014 the FDA approved Evzio (naloxone hydrochloride) as an emergency treatment for known or suspected opioid overdose.

Evzio delivers a single naloxone 0.4 mg dose via a hand-held auto-injector that can be carried in a pocket or stored in a medicine cabinet in a caregiver's home.

Another plus in an emergency situation -- when Evzio is turned on, it provides verbal instructions to the user. This is an obvious advantage in a stressful, emergency situation that a lay-person might encounter.

Because naloxone may not work as long as the opioid, and a return of slowed breathing may occur, a second repeat dose may be needed after 2 to 3 minutes until emergency help arrives.

How to Use Evzio Autoinjector

Read the "Instructions for Use" that comes with Evzio when you get it from the pharmacy or clinic. Evzio has built-in voice instructions to help guide administration, and directions are on the label, too.

When you need to use Evzio for an overdose:

  1. Pull Evzio from the outer case.
  2. Pull off the RED safety guard.
  3. Place the BLACK end of Evzio against the outer thigh. May administer through clothing if necessary.
  4. Press firmly and hold in place for 5 seconds.
  5. After using Evzio, get emergency medical help (call 911) right away. If symptoms return, another injection may be needed every 2 to 3 minutes.
  6. The Evzio Autoinjector cannot be reused; to re-administer another dose a new Evzio case must be activated.

Narcan Nasal Spray in Two Strengths

In November 2015 Narcan Nasal Spray 4 mg became available as the first FDA-approved nasal spray version of naloxone. A 2-mg strength was approved in Jan 2017. The 2-mg dose is for opioid-dependent patients expected to be at risk for severe opioid withdrawal in situations where there is a low risk for accidental or intentional opioid exposure by household contacts.

Narcan Nasal offers an advantage to the lay-person as, like Evzio, it is user-friendly and is easily carried in a purse or pocket or stored in the home.

In clinical studies, one dose of Narcan Nasal 4 mg resulted in similar levels to intramuscular (IM) injected naloxone 0.4 mg/mL and at roughly the same time.

The generic version -- naloxone nasal spray from Teva Pharmaceuticals -- was FDA-approved in 2019.

How to Use Narcan Nasal Spray

Narcan Nasal Spray can be used for adults or children. The drug is sprayed into one nostril while the person is lying on their back. To use:

  1. Remove the Narcan Nasal Spray from box. DO NOT prime the device before administering. Place your thumb on the plunger bottom and your first and middle fingers on either side of nozzle.
  2. Tilt the person’s head back and provide neck support with your hand.
  3. Gently insert the nozzle tip in one nostril until your fingers on either side of the nozzle are against the bottom of the person’s nose. Press the plunger firmly to give the full dose.
  4. Get emergency medical help right away after giving the first dose of Narcan Nasal Spray. Rescue breathing or CPR may be given while waiting for emergency medical help.
  5. If symptoms return, give another dose in the other nostril after 2 to 3 minutes using a new Narcan Nasal Spray in alternate nostrils with each dose until emergency medical assistance arrives.

Fully review directions enclosed in the box when you receive the medication; do not wait until an emergent situation.

Naloxone Side Effects

Common naloxone side effects may include symptoms of opioid withdrawal such as:

  • anxiety or agitation
  • sweating
  • nausea or vomiting
  • runny nose
  • high blood pressure
  • shivering

Acute withdrawal from chronic opioid use may also result in seizures, pain, and elevated heart rate.

While naloxone will reverse some, but not all, symptoms caused by a tramadol (Ultram, ConZip) overdose, the risk of seizures is also increased and may require treatment with an anti-seizure medication.

Reversal of respiratory depression caused by partial agonists or mixed agonists/antagonists, such as buprenorphine may be incomplete. Larger or repeat naloxone doses may be required.

Opioid Withdrawal Symptoms

In patients who are opioid-dependent, withdrawal symptoms can occur abruptly after administration of naloxone.

Sudden opioid withdrawal symptoms may include:

  • Body aches, diarrhea, increased heart rate
  • Fever, runny nose, sneezing
  • Goose bumps
  • Sweating, yawning, nausea or vomiting
  • Nervousness, restlessness or irritability
  • Shivering, trembling
  • Stomach cramping, weakness, increased blood pressure

Who's At Risk?

It isn't surprising that many people involved in prescription and illegal drug misuse and overdose situations are hesitant to call for emergency help due to legal concerns.

However, many states have implemented "Good Samaritan" laws which allow first responders of any kind, including family and friends, to administer naloxone without prior approval from a doctor. Most states have passed legislation to improve layperson access to naloxone. However, laws can vary by state, particularly with regard to immunity from prosecution if found with possession of controlled substances.

An opioid prescribing guideline from the CDC and Surgeon General notes that healthcare providers should consider offering naloxone when prescribing opioids to patients at elevated overdose risk, including:

  • patients with a history of overdose
  • patients with a history of substance (opioid) use disorder; misusing prescription opioids (for example, oxycodone or hydrocodone); or heroin, fentanyl, or carfentanil
  • patients taking benzodiazepines or alcohol with opioids
  • patients at risk for returning to a high dose to which they are no longer tolerant (e.g., patients recently released from prison or being discharged from opioid detoxification that does not include ongoing use of methadone, buprenorphine, or naltrexone).
  • patients taking higher dosages of prescription opioids (≥50 morphine milligram equivalents [MME] per day) for pain

Probuphine and Sublocade: Newer Options for Opiate Dependence

While Narcan can save a life from an overdose, a multi-pronged treatment plan is needed to rescue patients from chronic misuse of opioids.

As an added weapon in the treatment of opiate addiction, the FDA approved Probuphine in May 2016 as the first buprenorphine implant for the maintenance treatment of opioid dependence.

Probuphine consists of four, one-inch-long rods that are implanted under the skin and provide a constant, low-level dose of buprenorphine for six months.

In studies, 63 percent of Probuphine-treated patients had no evidence of illicit opioid use throughout the six months of treatment – similar to the 64 percent of those who responded to sublingual (under the tongue) buprenorphine alone.

Sublocade (buprenorphine) is also available as a once-monthly injectable partial opioid agonist formulation for the treatment of opioid use disorder (OUD). Sublocade, from Indivior, was FDA-approved in November 2017.

Related: Drugs Used to Treat Opiate Dependence

The Path Forward in Saving Lives

Prescription opioid drug addiction is a domestic threat unlike any other in the US. Concerted efforts from family, friends, health care providers, first-responders, and patients themselves are needed to combat this epidemic.

New, more user-friendly antidotes to reverse an opioid overdose are available, but accessibility for all parties is needed. Patients and caregivers should discuss with their healthcare provider whether or not the quick availability of a naloxone product makes sense in their situation, before an emergency occurs.

Individual medical advice should always come from your healthcare provider, but to keep up-to-date with the latest news, or to voice questions or concerns, consider joining the Opiate Dependence Support Group on We look forward to your contributions.

Finished: Know Your Naloxone: Save a Life

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